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Angiotensin-converting enzyme inhibition enhances a subthreshold stimulus to elicit delayed preconditioning in pig myocardium

Jaberansari, MT; Baxter, GF; Muller, CA; Latouf, SE; Roth, E; Opie, LH; Yellon, DM; (2001) Angiotensin-converting enzyme inhibition enhances a subthreshold stimulus to elicit delayed preconditioning in pig myocardium. J AM COLL CARDIOL , 37 (7) 1996 - 2001.

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Abstract

OBJECTIVES We assessed the effect of angiotensin-converting enzyme (ACE) inhibition in combination with a subthreshold preconditioning (PC) stimulus to elicit delayed preconditioning against infarction in pig myocardium.BACKGROUND Bradykinin triggers early PC. Angiotensin-converting enzyme inhibitors increase local bradykinin levels via inhibition of kinin breakdown and have been shown in experimental studies to augment early protection afforded by PC. A role for bradykinin in eliciting delayed PC has not so far been identified.METHODS We used a two-day protocol. On day 1 (dosed chest), pigs were either sham-operated (group 1) or preconditioned, using balloon catheter inflation of the left anterior descending (LAD) coronary artery, with either a full (4 x 5 min PC, group 2) or subthreshold PC stimulus (2 x 2 min PC, group 3). Additional soups were pre-treated with perindoprilat (0.06 mg/kg i.v.) before sham (group 4) or subthreshold PC (group 5). On day 2 (open chest), all pigs were subjected to 40 min occlusion of the LAD followed by 3 h of reperfusion. Infarct size was determined by tetrazolium staining.RESULTS Group 1 had a mean infarct size of 42.8 +/- 3.2% of the risk zone. Preconditioning with 4 X 5 min reduced the infarct size to 19.5 +/- 3.9% (p < 0.05). Groups 3 and 4 had infarct sizes not statistically different from group 1. However, combining perindoprilat with subthreshold PC resulted in a significant limitation of the infarction (18.4 +/- 3.1% p < 0.05), comparable with group 2.CONCLUSIONS This is the first study to show that ACE inhibition can augment a mild ischemic stimulus to induce a protected state 24 h later. (J Am Coll Cardiol 2001;37:1996-2001) (C) 2001 by the American College of Cardiology.

Type:Article
Title:Angiotensin-converting enzyme inhibition enhances a subthreshold stimulus to elicit delayed preconditioning in pig myocardium
Keywords:B-2 RECEPTOR ACTIVATION, INFARCT SIZE, BRADYKININ ANTAGONIST, NITRIC-OXIDE, HEART, PROTECTION, REDUCTION, RABBIT, RAMIPRILAT, ISCHEMIA
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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